title: PICOT is a critical regulator of cardiac hypertrophy and cardiomyocyte contractility.
abstract: PICOT (PKC-interacting cousin of thioredoxin) was previously shown to inhibit the development of cardiac hypertrophy, concomitant with an increase in cardiomyocyte contractility. To explore the physiological function of PICOT in the hearts, we generated a PICOT-deficient mouse line by using a gene trap approach. PICOT(-/-) mice were embryonic lethal indicating that PICOT plays an essential role during embryogenesis, whereas PICOT(+/-) mice were viable with no apparent morphological defects. The PICOT protein levels were reduced by about 50% in the hearts of PICOT(+/-) mice. Significantly exacerbated cardiac hypertrophy was induced by pressure overload in PICOT(+/-) mice relative to that seen in wild type littermates. In line with this observation, calcineurin-NFAT signaling was greatly enhanced by pressure overload in the hearts of PICOT(+/-) mice. Cardiomyocytes from PICOT(+/-) mice exhibited significantly reduced contractility, which may be due in part to hypophosphorylation of phospholamban and reduced SERCA activity. These data indicate that the precise PICOT protein level significantly affects the process of cardiac hypertrophy and cardiomyocyte contractility. We suggest that PICOT plays as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator.
authors.affiliation: Global Research Laboratory and Department of Life Science, Gwangju Institute of Science and Technology, Buk-Gu, Gwangju, South Korea. hscha@gist.ac.kr
authors.forename: Hyeseon
authors.initials: H
authors.lastname: Cha
authors.forename: Ji Myoung
authors.initials: JM
authors.lastname: Kim
authors.forename: Jae Gyun
authors.initials: JG
authors.lastname: Oh
authors.forename: Moon Hee
authors.initials: MH
authors.lastname: Jeong
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Jaeho
authors.initials: J
authors.lastname: Park
authors.forename: Hyeon Joo
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Byung Keon
authors.initials: BK
authors.lastname: Park
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Lee
authors.forename: Dongtak
authors.initials: D
authors.lastname: Jeong
authors.forename: Dong Kwon
authors.initials: DK
authors.lastname: Yang
authors.forename: Oliver Y
authors.initials: OY
authors.lastname: Bernecker
authors.forename: Do Han
authors.initials: DH
authors.lastname: Kim
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Park
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D006321:Heart / Q000196:embryology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000235:genetics; D011490:Protein Disulfide Reductase (Glutathione); D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D011490:Protein Disulfide Reductase (Glutathione); D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C498606:Txnl2 protein, mouse